Variant 2-86765955-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The ENST00000283632.5(RMND5A):c.785T>C(p.Ile262Thr) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000821 in 1,461,876 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000082 ( 0 hom. )

Consequence

RMND5A
ENST00000283632.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 8.02

Variant links:

Genes affected

RMND5A (HGNC:25850): (required for meiotic nuclear division 5 homolog A) Predicted to enable metal ion binding activity and ubiquitin protein ligase activity. Predicted to contribute to ubiquitin-protein transferase activity. Predicted to be involved in proteasome-mediated ubiquitin-dependent protein catabolic process and protein polyubiquitination. Located in cytoplasm and nucleoplasm. Part of ubiquitin ligase complex. [provided by Alliance of Genome Resources, Apr 2022]

RMND5A links:

RMND5A (HGNC:):

RMND5A links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RMND5A	NM_022780.4 linkuse as main transcript	c.785T>C	p.Ile262Thr	missense_variant	6/9	ENST00000283632.5	NP_073617.1	Q9H871-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RMND5A	ENST00000283632.5 linkuse as main transcript	c.785T>C	p.Ile262Thr	missense_variant	6/9	1	NM_022780.4	ENSP00000283632.4		Q9H871-1
RMND5A	ENST00000472843.5 linkuse as main transcript	n.187T>C		non_coding_transcript_exon_variant	2/5	2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000438

AC:

AN:

251370

Hom.:

AF XY:

0.0000221

AC XY:

AN XY:

135844

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000318

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000821

AC:

AN:

1461876

Hom.:

Cov.:

AF XY:

0.00000413

AC XY:

AN XY:

727238

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000246

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

8.99e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000508

Hom.:

Bravo

AF:

0.0000151

ExAC

AF:

0.00000824

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Oct 29, 2021

The c.785T>C (p.I262T) alteration is located in exon 6 (coding exon 6) of the RMND5A gene. This alteration results from a T to C substitution at nucleotide position 785, causing the isoleucine (I) at amino acid position 262 to be replaced by a threonine (T). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.90

BayesDel_addAF

Pathogenic

0.19

BayesDel_noAF

Pathogenic

0.34

CADD

Uncertain

DANN

Uncertain

0.99

DEOGEN2

Benign

0.11

Eigen

Uncertain

0.20

Eigen_PC

Uncertain

0.35

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Uncertain

0.92

M_CAP

Benign

0.0083

MetaRNN

Uncertain

0.47

MetaSVM

Benign

-0.73

MutationAssessor

Benign

1.9

MutationTaster

Benign

1.0

PrimateAI

Pathogenic

0.92

PROVEAN

Uncertain

-3.2

REVEL

Uncertain

0.38

Sift

Benign

0.10

Sift4G

Benign

0.14

Polyphen

0.065

Vest4

0.90

MutPred

0.55

Loss of stability (P = 0.0526);

MVP

0.37

MPC

1.6

ClinPred

0.29

GERP RS

5.4

Varity_R

0.17

gMVP

0.74

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over